Mucus-derived glycans are inhibitory signals for Salmonella Typhimurium SPI-1-mediated invasion
Year: 2025
Type: article
Abstract: Mucus forms a critical barrier against enteric pathogens like Salmonella enterica serovar Typhimurium. While in vivo studies indicate that secreted, gel-forming mucins and specifically core 3 glycosylation are protective against S. Typhimurium, the molecular mechanisms involved remain unclear. Here, we demonstrate that native intestinal mucins inhibit Salmonella invasion of colonic epithelial cells by downregulating the type 3 secretion system through suppression of the key virulence regulator, HilD. Our study identifies mucin glycans and specific mucin sugars, namely N-acetyl galactosamine and N-acetyl glucosamine, as the components responsible for mucin's anti-virulence effect, likely via functional or direct interaction with HilD's putative carbohydrate-binding domain. Notably, we find that the native presentation of these sugars is important for activity. These insights provide a mechanistic foundation for mucin-based strategies to combat enteric infections and, given the prevalence of homologous AraC-type regulators in other pathogens, suggest mucins' potential as broad-spectrum anti-virulence agents.
Source: Cell Reports
Language: English
Subfield: Endocrinology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,620
Funders: National Science Foundation, Foundation for the National Institutes of Health, U.S. Department of Energy, Deutsche Forschungsgemeinschaft, National Institutes of Health, Multidisciplinary University Research Initiative, National Institute of General Medical Sciences, National Institute of Environmental Health Sciences, Army Research Office, Institute for Collaborative Biotechnologies
Awards: G1018384621, G1148400999, G1280801758, Collaborative Research: MIM: Learning how mucus shapes and maintains microbiomes, G192994814, G220646820, G2877706843, G3437827786, G443779809, G5357099631, G582811279, Synthetic mucins in epithelial models to probe virus-mucin interactions, G6042108000, G608057831, G6136270856, G613990440, SFB 1449: Dynamische Hydrogele an Biogrenzflächen, Pre-Doctoral Training in Biological Sciences, G7452299184, G783422742, G8415477955, G9000110780, G9000219151, G9000300833, G960073642, THE CENTER FOR PLANT AND MICROBIAL COMPLEX CARBOHYDRATES AT THE UNIVERSITY OF GEORGIA COMPLEX CARBOHYDRATE RESEARCH CENTER
OpenAlex ID: W4414478140